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Parkinson’s disease (PD) is a chronic and progressive neurodegenerative disease of unknown etiology. The pathology involves a degeneration of dopaminergic neurons of the substantia nigra with consequent dopamine (DA) deficiency and neurodegeneration of striatal neurons. The most effective treatments target compensation for the DA deficit. Among the different strategies applied, the most used is pharmacological substitutive treatment with levodopa (L-DOPA). Nevertheless, all current treatments may be considered palliative and not curative. Here we review the latest advances in research and preclinical investigation in cell restorative therapy by using slice tissue cultures as a model of PD. This chapter describes in detail the main organotypic models used to study the cellular and molecular mechanisms leading to dopaminergic degeneration. In particular, we move from the simplest organotypic co-cultured model of the substantia nigra-striatum-cortex to the unique slice of nigro-striatal slice used to study endogenous neurogenesis or viral vector-mediated overexpression of -synuclein in midbrain slices. We discuss the possibility of using such models to induce adult neurogenesis by combining pharmacological treatments or for preclinical studies in cell transplantation. The strategies in place thus far to restore the dopaminergic system in PD are pharmacological treatments, such as administration of L-DOPA, cell restorative therapy by gene therapy, or cell therapy by stem cell grafting. The main pharmacological treatment for PD symptoms today is the administration of L-DOPA, especially in the first stages of disease. L-DOPA, a DA precursor, acts to counteract the DA deficit in neurons. However, the beneficial effect of the drug lasts only a few years with disease progression and loss of efficacy, followed by onset of secondary effects such as on–off phenomena, dyskinesia, and psychosis. Moreover, recent studies in an animal model (Muller et al., 2004) suggest a toxic effect of prolonged L-DOPA treatment; thus, pharmacological investigation is devoted to studying new compounds or new therapeutic strategies. Inhibitors of an alternative metabolic route of DA such as entacapone and tolcapone are also used in pharmacological treatment (Linazasoro, 2008). The administration of several neurotrophic factors has been intensively investigated in a rat model as a possible therapeutic strategy for PD (Grandoso et al., 2007). In particular, glial

Utility of Organotypic Slices in Parkinson's Disease Research